Immunoconjugates and humanized antibodies specific for B-cell lymphoma and leukemia cells
A chimeric LL2 monoclonal antibody is described in which the complementarity determining regions (CDRs) of the light and heavy chains of the murine LL2 anti-B-lymphoma, anti-leukemia cell monoclonal antibody has been recombinantly joined to the human kappa and IgG1 constant region domains, respectively, which retains the immunospecificity and B-cell lymphoma and leukemia cell internalization capacity of the parental murine LL2 monoclonal antibody, and which has the potential of exhibiting reduced human anti-mouse antibody production activity. A humanized LL2 monoclonal antibody is described in which the CDRs of the light and heavy chains have been recombinantly joined to a framework sequence of human light and heavy chains variable regions, respectively, and subsequently linked to human kappa and IgG1 constant region domains, respectively, which retains the immunospecificity and B-lymphoma and leukemia cell internalization capacities of the parental murine and chimeric LL2 monoclonal antibodies, and which has the potential for exhibiting reduced human anti-mouse antibody production activity. Vectors for producing recombinant chimeric and humanized chimeric monoclonal antibodies are provided. Isolated DNAs encoding the amino acid sequences of the LL2 variable light and heavy chain and CDR framework regions are described. Conjugates of chimeric and humanized chimeric LL2 antibodies with cytotoxic agents or labels find use in therapy and diagnosis of B-cell lymphomas and leukemias. 
Epidemiology of Primary CNS Lymphoma
In the beginning of the nineties the National Cancer Institute Surveillance, Epidemiology, and End Results Program calculated the incidence of primary central nervous system non-Hodgkin’s lymphoma (PCNSL) as 1:100 000. The incidence of PCNSL has been increasing since the seventies in immunocompetent patients. The main increase, however, is taking place since the mid-eighties and is due to the increase of immunodeficieny and immunosuppression. The risk is 2–6% in AIDS patients according to clinical data and will probably further increase with the length of survival in these patients. Transplant patients carry a risk of 1–5% to develop a PCNSL. The risk is 1–2% for renal, and 2–7% for cardiac, lung or liver transplant recipients. Patients with congenital immune deficiency have a risk of 4%. PCNSL may also present as a secondary malignancy. 
The incidence of intermediate and high grade B-cell non-Hodgkin’s lymphomas in HIV-infected individuals is approximately 60 times greater than in the general population. These AIDS-related lymphomas (AIDS-NHL) are a late manifestation of HIV infection and may increase in frequency as patients live longer with highly active antiretroviral therapy and effective prophylaxis of opportunistic infections. AIDS-NHL have unique clinical and pathological features that are different from non-Hodgkin’s lymphomas in the general population. Histologically AIDS-NHL are either high (2/3) or intermediate (1/3) grade lymphomas. Clinically AIDS-NHL have a preponderance for extranodal involvement with central nervous system being the most common site for this. In addition to the clinical and pathological features of AIDS-NHL, a current knowledge of their pathogenesis and treatment options are presented in this review. 
In Vivo Antitumor Activity of Metal Silver and Silver Nanoparticles in the L5178Y-R Murine Lymphoma Model
Aims: To evaluate the antitumor potential of metal silver and polyvinilpyrrolidone nanoparticle-encapsulated silver on L5178Y-R murine lymphoma cell growth and survival of tumor-bearing mice.
Study Design: In vitro and in vivo (pre-clinical) study.
Place and Duration of Study: Universidad Autónoma de Nuevo León, Facultad de Ciencias Biológicas, Departamento de Microbiología e Inmunología, San Nicolás de los Garza, N.L., México, from January 2009 to December 2011.
Methodology: Concentration-response cell viability assay was performed in vitro and mice survival studies were done using a L5178Y-R tumor-bearing mouse model. The PROBIT regression analysis was performed to determine the in vitro LC50. In vivo survival distributions were calculated by Kaplan-Meier and Cutler-Ederer analysis, and survival curves comparisons and hypothesis testing was done using the log-rank method.
Results: Metal silver induced up to 100% L5178Y-R cells cytotoxicity, with an LC50 of 1.8 X 10-8 M, whereas silver nanoparticles caused up to 78% cytotoxicity, with an LC50 of 14.4 X 10-8 M. In addition, Intramuscular administration of metal silver and silver nanoparticles administered at the time of tumor injection significantly (P = .05) increased mice survival, where 70% and 60% of mice survived at day 35 respectively, as compared with such treatments administered 7 days after tumor induction (55% and 25% survival respectively); vincristine treatment caused 50% mice survival and tumor-bearing control mice had 20% survival. These results open further approaches on treating several types of cancer using free and nanoparticle-encapsulated silver-based therapies. 
Lymphoma with Bilateral Contrast Enhancement and Restricted Diffusion of Multiple Cranial Nerves in MRI
We present a 50-year-old female with paresthesia on the right side of her face, facial asymmetry, hearing loss, and difficulty in walking. After clinical and radiological evaluations, non-Hodgkin lymphoma type B has been diagnosed. Cranial MRI revealed contrast enhancement of 3rd, 5th, 7th, and 8th cranial nerves bilaterally. Diffusion-weighted imaging (DWI) revealed prominent hyperintense symmetric cranial nerves involvement with corresponding signal reduction on Apparent Diffusion Coefficient (ADC) maps. In lymphoma cases, any of the 12 cranial nerves may be affected. Although such clinical phenomena have been described previously, this is the first patient to demonstrate restricted diffusion related to multiple cranial nerves. 
 Leung, S.O. and Hansen, H., Immunomedics Inc, 1998. Immunoconjugates and humanized antibodies specific for B-cell lymphoma and leukemia cells. U.S. Patent 5,789,554.
 Schabet, M., 1999. Epidemiology of primary CNS lymphoma. Journal of neuro-oncology, 43(3), pp.199-201.
 Tulpule, A. and Levine, A., 1999. AIDS-related lymphoma. Blood reviews, 13(3), pp.147-150.
 Lara-González, J. H., Gomez-Flores, R., Tamez-Guerra, P., Monreal-Cuevas, E., Tamez-Guerra, R. and Rodríguez-Padilla, C. (2013) “In Vivo Antitumor Activity of Metal Silver and Silver Nanoparticles in the L5178Y-R Murine Lymphoma Model”, Journal of Advances in Medicine and Medical Research, 3(4), pp. 1308-1316. doi: 10.9734/BJMMR/2013/3108.
 Rasul, S., Abdulkadir, K., Özge, A. and Alpay, A. (2015) “Lymphoma with Bilateral Contrast Enhancement and Restricted Diffusion of Multiple Cranial Nerves in MRI”, International Neuropsychiatric Disease Journal, 3(2), pp. 69-73. doi: 10.9734/INDJ/2015/15303.